Essential hypertension is typically thought to attack the brain late in its course, primarily through stroke. Accumulating evidence from both human and animal studies, though, shows that essential hypertension is associated with mild cognitive deficits, altered cerebral blood flow, decreases in grey matter volume, altered sympathetic nervous system function, and signs of premature brain aging. This evidence suggests that the brain is an early target of the disease, and, perhaps, the initial target. We propose to establish this point by examining pre-hypertensive individuals to establish that the brain sequelae of the disease are present prior to diagnostic levels of high blood pressure. We propose a cross sectional study of 250 participants followed by a 2 year longitudinal study of 200 participants with initial blood pressures in the pre-hypertensive range. Presence of brain sequelae in pre-hypertensive individuals will suggest that the currently accepted view is no longer tenable, the view that the brain is only affected late in the disease. Longitudinal results should indicate whether brain alterations predict later blood pressure or both brain and vascular effects of the disease occur in parallel. Risk factors associated with hypertension will be closely examined to see if such factors may implicate co-occurring pathology rather than hypertension in the induction of brain alterations. Successful completion of the project should direct clinical attention toward early sequelae of essential hypertension in both the brain and vasculature. PUBLIC HEALTH RELEVANCE: This project is designed to show that brain structure and function is altered by essential hypertension even prior to the appearance of hypertensive levels of blood pressure. Current medical thought suggests that essential hypertension is a vascular disease that late in its course can interact with atherosclerosis to pose a high risk for stroke. Current evidence and that proposed in this project suggest in contrast that the brain is altered early in the course of the disease. Recognition of this should direct clinical intervention to the reversal of these brain effects in addition to the reduction of peripheral blood pressure. The significance of such a re-orientation is clear given the pandemic proportions of essential hypertension.